Our understanding of human health and the development of new preventive and therapeutic approaches requires the integration in the study of physiology and pathology of the constant exposure of the organism to the microbiota and to evaluate physiology and pathology as states of the whole human metaorganism. In collaboration with geneticists, molecular biologists and bacteriologists, our research is conducted in a multidisciplinary manner combining, cellular immunology, microbiology and genomic approaches. Over the past fiscal year, our work further explored the role of the microbiota in the control of host immunity at barrier sites including the gut, skin and lung. Our work was the first to reveal the adjuvant role of the microbiota in the induction of protective immunity to pathogens and in the context of vaccine. Current work from our group explores the role of defined commensal species in the regulation of skin and gut immunity. In particular, our research explores the mechanism by which defined commensal species or bacterial products control tissue immune homeostasis and promote adaptive immune responses in the context of steady state, infection and tissue inflammation. Notably our work identified key antigen presenting cells responsible for the mediation of responses to commensals. In addition, our group addresses how a dysregulation in the composition of commensal populations and aberrant responses against commensals during infection can lead to pathogenic responses (e.g pathogenic consequence of infections, Crohns disease, Psoriasis). These studies are currently done in collaboration with Drs. Giorgio Trinchieri (NCI), Julie Segre (NHGR) and Karen Frank (Clinical Center). Future directions aim at further integrating patients and clinical isolates to the exploration of these questions.